Studies have been designed to use exhaled NO to target the treatment of asthma, and recently a Cochrane review has concluded that, at present, defining the dose of inhaled corticosteroids based on exhaled NO cannot be routinely advocated (¹). It has also been concluded in an American Thoracic Society/European Respiratory Society (ATS/ERS) document on standardizing end-points for clinical asthma trials and clinical practice that in clinically stable asthma the exhaled NO (F_ENO) values are generally higher than in healthy control subjects (²). Therefore, reference NO values are of limited use in guiding the clinician in the treatment of patients with asthma. In the present case study it is demonstrated why the F_ENO_0.05 (fractional concentration of exhaled NO in the gas phase, 0.05 L/s) remains high after treatment and that NO parameters from non-linear modelling are clinically useful.

A male subject, 30 years of age, with the diagnosis of atopic asthma since childhood was investigated. The baseline NO analysis was done without inhaled corticosteroids (ICS). After one week on 800 microgram ICS twice a day, F_ENO values were obtained again with multiple flow rates using a CLD 88sp NO analyser (ECO Medics AG, Switzerland). The NO production of the respiratory system was computed with the non-linear NO model by Högman and Meriläinen (³).

There was a dramatic decrease in F_ENO_0.05 of 58% in 1 week of treatment, but it was still higher than reference values for healthy controls (⁴). In Figure 1 it can be seen that there was no change in airway diffusion capacity of NO (D_awNO) due to ICS. D_awNO is known to be increased in atopic rhinitis and atopic asthma (⁵) and not affected by ICS (⁶). The alveolar NO levels (C_ANO) were low. Noteworthily, the airway tissue content (C_awNO) was reduced by ICS to levels presented for healthy controls (⁴).

When the NO parameters are known, the non-linear model can be used to calculate the F_ENO_0.05 (³). Different values of C_awNO, D_awNO, and C_ANO can be fed into a Microsoft Office Excel spreadsheet, where NO volumes at different expiratory flow rates are visualized and F_ENO for specific flow rates are given. For the illustration, typical NO values in health, atopy, and asthma are shown in Table I. Since D_awNO is not affected by ICS, this value can be used in the calculations together with C_awNO and C_ANO values for healthy controls (³). This calculation will result in a personal best or target value of F_ENO_0.05 to be used during treatment. This target value of F_ENO_0.05 was quite similar to the value after 1 week of treatment in this case study and in a group of asthmatics in a study by Silkoff et al. (⁶).

One week of ICS reduced the C_awNO to reference levels for healthy controls. The F_ENO_0.05 level stayed elevated, which is due to the lack of change in D_awNO, known to be high in allergic asthma (⁵) and not affected by ICS in asthma (⁶).

In a study by Smith et al. (⁷) it was concluded that optimum F_ENO levels were best established by using oral rather than inhaled steroid treatment and that values were higher than reference values even though asthma was well controlled. The finding in this case study gives other solutions to finding the personal best value of F_ENO_0.05. One solution is to use the non-linear NO model and follow the ICS treatment with C_awNO. Another solution is to determine the D_awNO for the patient and then use the C_awNO and C_ANO for healthy controls to identify a target value of F_ENO_0.05. In our patient it was 33 ppb. The F_ENO value can then be followed with a simple portable NO device in primary care.

The importance of controlling F_ENO has been shown in children, where airway hyper-responsiveness improved with lower F_ENO (⁸), and in difficult-to-treat asthma, where an increased NO value was a predictor of accelerated decline in lung function (⁹). Therefore NO values should preferentially be monitored in allergic asthma in both children and adults, and D_awNO is useful for targeting F_ENO_0.05. Further studies have to be designed to evaluate the personal best NO value by an approach presented in this case report.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.